The clubs have not met in the competition since 1971 but are familiar foes outside the Premier League.
The FA Cup now represents the only hope of winning silverware for both Arsene Wenger and Pep Guardiola, with both managers under pressure after seeing their Premier League and Champions League hopes fade.
Here are some of their most memorable cup meetings since the turn of the century.
Man City 1 Arsenal 2 | League Cup, 2004
Arsene Wenger celebrated confirmation of a new contract which committed him to Arsenal until 2008 as goals from Robin van Persie and Daniel Karbassiyoon took the Gunners into the last 16. Robbie Fowler pulled one back for City.
Man City 3 Arsenal 0 | League Cup, 2009
Carlos Tevez, Shaun Wright-Phillips and Vladimir Weiss were on target as City maintained the dream of ending their 33-year trophy drought by beating Arsenal in a League Cup contest at Eastlands.
Arsenal 0 Man City 1 | League Cup, 2011
Argentina striker Sergio Aguero came off the bench to fire City into the semi-finals of the League Cup, slotting home with seven minutes left following a sweeping counter-attack.
Arsenal 3 Man City 0 | Community Shield, 2014
Back at the scene of their FA Cup triumph, the Gunners tore into a lacklustre City side in the first half, taking control of the league champions with goals from Santi Cazorla and Aaron Ramsey.
Substitute Olivier Giroud cracked home a third from 25 yards on the hour.
Additional reporting by the Press Association.